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Cancer Immunol Immunother. 2018 Mar;67(3):423-434. doi: 10.1007/s00262-017-2090-z. Epub 2017 Dec 4.

Therapeutic reduction of cell-mediated immunosuppression in mycosis fungoides and Sézary syndrome.

Author information

1
Department of Dermatology, University of Pittsburgh, Suite 500.68 Medical Arts Building, 3708 Fifth Avenue, Pittsburgh, PA, 15213, USA.
2
UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
3
Department of Dermatology, Columbia University, New York, NY, USA.
4
Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
5
Center for Biological Imaging, University of Pittsburgh, Pittsburgh, PA, USA.
6
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
7
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
8
Department of Dermatology, University of Pittsburgh, Suite 500.68 Medical Arts Building, 3708 Fifth Avenue, Pittsburgh, PA, 15213, USA. lof2@pitt.edu.
9
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA. lof2@pitt.edu.
10
UPMC Hillman Cancer Center, Pittsburgh, PA, USA. lof2@pitt.edu.
11
Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA. lof2@pitt.edu.
12
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA. lof2@pitt.edu.

Abstract

Tumor progression is associated with progressive immunosuppression mediated in part by T regulatory cell(s) (Treg) and/or myeloid-derived suppressor cell(s) (MDSC). Development of strategies to reduce populations of immune cells with suppressive function in cancer patients may enable the induction or recovery of immunity against tumor cells, which may limit or reverse disease progression. With a goal of developing Treg and MDSC neutralizing strategies to treat mycosis fungoides (MF) and Sézary syndrome (SzS), we determined the association between disease stage and suppressor cell populations in patients with MF/SzS, including those responding to therapy. We found elevations in Treg populations, across Treg subtypes, in patients with SzS, and these Treg markedly suppressed proliferation of autologous CD4+CD25- responder T cells. Interestingly, while MDSC numbers were not increased in MF/SzS patients, MDSC from patients with stage IB and above produced significantly more reactive oxygen species than those from stage IA MF patients and control cohorts. Therapy with the CD25-targeting agent denileukin diftitox or IFN-α2b was associated with a reduction in Treg numbers or MDSC function, respectively. These studies identify potential mechanisms of action for these therapies and support the development of coordinated strategies targeting both Treg and MDSC activities in patients with MF/SzS.

KEYWORDS:

Cutaneous T-cell lymphoma; Mycosis fungoides; Myeloid-derived suppressor cells; Sézary syndrome; T regulatory cells

PMID:
29204699
DOI:
10.1007/s00262-017-2090-z
[Indexed for MEDLINE]

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